Yersinia pestis is the causative agent of plague. At least three great pandemics of plague have been recorded in history, which killed nearly 200 million people. Plague is a zoonotic disease typically transmitted by the bite of an infected flea. Natural reservoirs for Y. pestis include rodents, squirrels and prairie dogs. Large reservoirs of Y. pestis currently exist on all major inhabited continents, except Australia (Sun et al., J Infect Dev Ctries 5(9):614-627, 2011). Plague is endemic to many parts of the world, including Africa, China, India, portions of South America and the southwestern United States (Yang et al., J Immunol 178:1059-1067, 2007; Leary et al., Microb Pathog 23:167-179, 1997). Recent epidemiological studies indicate that worldwide there are approximately 4,000 human plague cases annually (Sun et al., J Infect Dev Ctries 5(9):614-627, 2011). Thus, plague remains a serious public health concern.
Plague most commonly presents as bubonic plague, characterized by the sudden onset of fever and painful swelling of lymph nodes (“buboes”) close to the flea bite. Prompt treatment with antibiotics is generally effective (Morton et al., Vaccine 22:2524-2532, 2004). However, bacteria can disseminate widely from the site of the flea bite and in some cases, infect the lung. If the lung is infected, plague can be transmitted in aerosols produced by coughing or sneezing, leading to outbreaks of primary pneumonic plague (Leary et al., Microb Pathog 23:167-179, 1997). Pneumonic plague is highly contagious and generally fatal (Morton et al., Vaccine 22:2524-2532, 2004). Since plague is highly infectious and can spread by aerosolization, Y. pestis is considered a potential biological weapon (Sun et al., J Infect Dev Ctries 5(9):614-627, 2011; Yang et al., J Immunol 178:1059-1067, 2007).